This is a proposal for an interdisciplinary program for basic research in problems of skin biology and pathology. The program project will involve seven principal areas with five in this application and two to be submitted later. 1. Correlated physiological and ultrastructural studies of the cutaneous microcirculation with especial emphasis on identifying structural parameters of sphincter regions in the microvasculature; 2. Development of new noninvasive methods to test the strength of healing surgical wounds with time; 3. Analysis of biochemical and functional properties of the basic (mature) protein of stratum corneum with especial reference to how this protein relates to cellular morphology and to cutaneous disease in instances where keratohyalin is absent; 4. Measurement of electrical conduction in the stratum corneum (SC) under conditions in which components of SC have been extracted; 5. Physiology, pharmacology, and pathophysiology of the eccrine sweat gland unit in man will be investigated to determine: 1. the locus and mechanism of secretory adaptation with heat acclimatization; 2. differences in cholinergic and adrenergic responsiveness in normal, allergic and atopic individuals; and 3. the applicability of iontophoresis as a method of delivery of drugs intradermally. 6. The analysis of structural and biochemical characteristics of inherited diseases of structural defects in collagen. 7. quantitative pharmacokinetics of percutaneous absorption in human skin. Part 1 of 7.